IFT20 is critical for collagen biosynthesis in craniofacial bone formation

Yamaguchi, Hiroyuki; Terajima, Masahiko; Kitami, Megumi; Wang, Jianbo; He, Li; Saeki, Makio; Yamauchi, Mitsuo; Komatsu, Yoshihiro

doi:10.1016/j.bbrc.2020.09.033

Cited by 14 publications

(16 citation statements)

References 47 publications

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“…Moreover, loss of IFT20 in CNC-derived mesenchymal cells disrupts the biosynthesis of collagen (a key element in bone mineralization) by increasing the FKBP65 chaperone level, resulting in poor-quality bone collagen, given that the FKBP65 chaperone regulates lysyl hydroxylase 2 activity, which plays an essential role in the collagen cross-linking process. In addition, IFT20 deletion also reduces the amount of collagen production due to dysfunction in endoplasmic reticulum to Golgi trafficking of collagen (Yamaguchi et al 2020). Taken together, these studies highlight the important functions of primary cilia in craniofacial development through regulating different signaling pathways.…”

Section: Primary Cilia In Craniofacial Developmentmentioning

confidence: 69%

Role of Primary Cilia in Bone and Cartilage

et al. 2021

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The primary cilium is a nonmotile microtubule-based organelle in most vertebrate cell types. The primary cilium plays a critical role in tissue development and homeostasis by sensing and transducing various signaling pathways. Ciliary proteins such as intraflagellar transport (IFT) proteins as well as ciliary motor proteins, kinesin and dynein, comprise a bidirectional intraflagellar transport system needed for cilia formation and function. Mutations in ciliary proteins that lead to loss or dysfunction of primary cilia cause ciliopathies such as Jeune syndrome and Ellis–van Creveld syndrome and cause abnormalities in tooth development. These diseases exhibit severe skeletal and craniofacial dysplasia, highlighting the significance of primary cilia in skeletal development. Cilia are necessary for the propagation of hedgehog, transforming growth factor β, platelet-derived growth factor, and fibroblast growth factor signaling during osteogenesis and chondrogenesis. Ablation of ciliary proteins such as IFT80 or IFT20 blocks cilia formation, which inhibits osteoblast differentiation, osteoblast polarity, and alignment and reduces bone formation. Similarly, cilia facilitate chondrocyte differentiation and production of a cartilage matrix. Cilia also play a key role in mechanosensing and are needed for increased bone formation in response to mechanical forces.

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Section: Primary Cilia In Craniofacial Developmentmentioning

confidence: 69%

Role of Primary Cilia in Bone and Cartilage

et al. 2021

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“…However, at present, little is known about how IFTs function when organizing bone ECM. In this regard, we have recently reported that IFT20 plays a pivotal in collagen biosynthesis by regulating, in part, telopeptidyl lysine hydroxylation and crosslinking in the craniofacial bone (Yamaguchi et al, 2020). This demonstrates that IFT20 participates in collagen post-translational modifications to control the 'quality' of collagen.…”

Section: Discussionmentioning

confidence: 95%

“…However, this can be explained by the following reasons. Recently, we have reported that IFT20 plays a pivotal role in regulation of collagen quality (Yamaguchi et al, 2020). Because IFT20 directly interacted with GMAP210 (Fig.…”

Section: Gmap210 Regulates Collagen Trafficking In Cnc-derived Osteoblastsmentioning

confidence: 94%

The molecular complex of ciliary and golgin protein is critical for skull development

Yamaguchi

Meyer

et al. 2021

Development

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Intramembranous ossification, which consists of direct conversion of mesenchymal cells to osteoblasts, is a characteristic process in skull development. One critical role of these osteoblasts is to secrete collagen-containing bone matrix. However, it remains unclear how the dynamics of collagen trafficking is regulated during skull development. Here, we reveal the regulatory mechanisms of ciliary and golgin proteins required for intramembranous ossification. During normal skull formation, osteoblasts residing on the osteogenic front actively secreted collagen. Mass spectrometry and proteomic analysis determined endogenous binding between ciliary protein IFT20 and golgin protein GMAP210 in these osteoblasts. Like in Ift20 mutant mice, disruption of neural-crest specific GMAP210 in mice caused osteopenia-like phenotypes due to dysfunctional collagen trafficking. Mice lacking both IFT20 and GMAP210 displayed more severe skull defects compared to either IFT20 or GMAP210 mutants. These results demonstrate that the molecular complex of IFT20 and GMAP210 is essential for the intramembranous ossification during skull development.

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“…Definitions of cephalometric landmarks and measurements are described in Tables 1, 2 34,35 . Immunofluorescent staining, H&E staining, Safranin‐O staining, and Picrosirius red staining were performed as previously described 33,36,37 . TUNEL assay was performed using Click‐iT Plus TUNEL Assay for In Situ Apoptosis Detection kit (Invitrogen; C10618).…”

Section: Methodsmentioning

confidence: 99%

“…34,35 Immunofluorescent staining, H&E staining, Safranin-O staining, and Picrosirius red staining were performed as previously described. 33,36,37 TUNEL assay was performed using Click-iT Plus TUNEL Assay for In Situ Apoptosis Detection kit (Invitrogen; C10618). Primary antibodies used in immunohistochemistry staining were as follows: BiP (1:100, Santacruz Biotechnology; Sc-13 968), CHOP (1:100, Santacruz Biotechnology; Sc-575), EGFP (1:1000, abcam; ab13970), and GMAP210 (1:200, LS Biosciences; LS-C20059).…”

Section: Skeletal Preparations Histological Analysis and Fluorescence...mentioning

confidence: 99%

Disruption of Trip11 in cranial neural crest cells is associated with increased ER and Golgi stress contributing to skull defects in mice

Yamaguchi

Meyer

et al. 2022

Developmental Dynamics

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Background Absence of Golgi microtubule‐associated protein 210 (GMAP210), encoded by the TRIP11 gene, results in achondrogenesis. Although TRIP11 is thought to be specifically required for chondrogenesis, human fetuses with the mutation of TRIP11 also display bony skull defects where chondrocytes are usually not present. This raises an important question of how TRIP11 functions in bony skull development. Results We disrupted Trip11 in neural crest‐derived cell populations, which are critical for developing skull in mice. In Trip11 mutant skulls, expression levels of ER stress markers were increased compared to controls. Morphological analysis of electron microscopy data revealed swollen ER in Trip11 mutant skulls. Unexpectedly, we also found that Golgi stress increased in Trip11 mutant skulls, suggesting that both ER and Golgi stress‐induced cell death may lead to osteopenia‐like phenotypes in Trip11 mutant skulls. These data suggest that Trip11 plays pivotal roles in the regulation of ER and Golgi stress, which are critical for osteogenic cell survival. Conclusion We have recently reported that the molecular complex of ciliary protein and GMAP210 is required for collagen trafficking. In this paper, we further characterized the important role of Trip11 being possibly involved in the regulation of ER and Golgi stress during skull development.

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IFT20 is critical for collagen biosynthesis in craniofacial bone formation

Cited by 14 publications

References 47 publications

Role of Primary Cilia in Bone and Cartilage

Role of Primary Cilia in Bone and Cartilage

The molecular complex of ciliary and golgin protein is critical for skull development

Disruption of Trip11 in cranial neural crest cells is associated with increased ER and Golgi stress contributing to skull defects in mice

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